Etiology Of Acute Kidney Injury Research Articles

#5618 IMPACT OF THE PATHOPHYSIOLOGY OF ACUTE KIDNEY INJURY IN PATIENTS AFFECTED BY COVID-19 ON CLINICAL OUTCOMES DIALYSIS AND DEATH

Abstract Background and Aims The Coronavirus Disease-19, COVID-19 caused by the Sars-Cov-2 virus has been associated with either asymptomatic and mild conditions or severe acute respiratory syndrome with generalized organ dysfunction and death. One of the most important is Acute Kidney Injury (AKI). It is acknowledged that AKI is multifactorial, as the most relevant factors for its development are the cytokine storm, metabolic stress, medication use, rhabdomyolysis, renal viral tropism, and multiple organ dysfunction. However, little is known about the impact of AKI's pathophysiology on its clinical outcome. Method Retrospective cohort study that evaluated the medical records of patients diagnosed with COVID-19 admitted to a Tertiary Public Hospital, from 06/01/2020 to 07/31/2021 from their admission until the outcome. The evaluation of renal function occurred through the variation of urinary output and serum creatinine measurement, and the diagnosis of AKI followed the 2012 KDIGO criteria. The occurrence of AKI was an inclusion criterion in the study. The nephrotoxic drug usage and the leak of clinical and laboratory data were exclusion criteria in the study. In addition to urine output and serum creatinine, the creatine phosphokinase, type 1 urine test concerning proteinuria and haematuria, cardiocirculatory and ventilatory parameters, and vasoactive, diuretic, antihypertensive and corticoid drugs usage were analysed. Univariate analysis was performed to identify whether the pathophysiological mechanisms of AKI (ischemic, cytokine storm- CS, rhabdomyolysis, renal viral tropism, or multiple organ failure- MOF) are associated with death. Results Until now, we have included 283 patients. There was a predominance of males (55.5%), Caucasian ethnicity (80.6%); median age was 64 years. Most patients were admitted to the ICU (85.1%). The predominant AKI was KDIGO 3 (56.9%). Regarding the different etiologies of AKI, Renal Viral Tropism was the most frequent (21.5%), followed by MOF (19.1%), Septic (16.6%), Mixed Renal Viral Tropism (16.2%), Ischemic (15.5%) and CS (10,9%). Regarding the CS, patients were more often admitted to the ICU (100%; p<0.001) made the least use of corticosteroids (51.6%; p>0.001) and diuretics (12.9%; p = 0.016), they made the most use of mechanical ventilation (100%), vasoactive drugs (100%) and dialysis (74.2%; p<0.001). Paradoxically, they were the most obese (67.74% p = 0.011), but had less hypertension (48.4%; p = 0.025), less previous cardiovascular disease (6.45% p = 0.01), and less dyslipidemia (9.68%; p = 0.012). In general, the mixed etiology markedly comes closest to the CS etiology, followed by the MOF. Patients who least needed dialysis were those with septic etiology (18.18%; p<0.001). Preliminary tests show an impressive mortality of 69.61%, which is associated with the AKI pathophysiological mechanisms (p<0.0001). CS (87.1%), MOF (87.0%), and Mixed Etiologies (89.1%) are the pathophysiological mechanisms associated with poor prognosis; and Viral Renal Tropism (54.3%), Sepsis (48.3%), and Ischemic Injury (34.1%) are the pathophysiological mechanisms related to the best outcomes. Conclusion AKI related to COVID-19 patients are mostly elderly, admitted to ICU, classified as KDIGO 3 and their mortality is notable. Nevertheless, the mortality and the need for dialysis depends on the pathophysiological mechanism their AKI, as CS, MOF, and Mixed Etiologies are the pathophysiological mechanisms associated with poorest prognosis; and Viral Renal Tropism, Sepsis, and Ischemic Injury are related to the best outcomes.

#3235 ELECTROLYTE DISORDERS IN COMMUNITY-ACQUIRED ACUTE KIDNEY INJURY

Abstract Background and Aims The kidney plays a decisive role in regulating the homeostasis of the internal environment. Acute kidney injury (AKI) compromises the kidney's ability to maintain this regulation intact, and the appearance of various electrolyte disorders is to be expected in this situation. There are few data in the literature that describe these alterations in patients with community-acquired AKI (CA-AKI). The purpose of this study is to analyze the incidence of electrolyte disorders in a cohort of patients with CA-AKI admitted to the nephrology service of a tertiary level hospital. Method This is a single-center, observational, longitudinal, and retrospective study based on a cohort of patients with CA-AKI admitted to the Nephology Service of a third level hospital from January 2010 to December 2018. We analyzed the incidence of changes in sodium, potassium, chloride, bicarbonate, calcium, and phosphorus in these patients and their clinical consequences during admission and follow-up after hospital discharge. Results A total of 639 patients were included in the final analyses. The mean age was 72,93±13,38 years. 61,7% were men. Charlson comorbidity index was 5,87 ±2,4 points. The length of stay was 11,63±10,14 days. In view of the Etiology of AKI, 72,1% had prerenal AKI and 27,9% non-prerenal. 436 patients had a history of previous chronic kidney disease (CKD) (68.23%). AKI KDIGO stages were: stage I, 105 cases (16.4%); stage II, 67 cases (10.5%); stage III 467 cases (63.1%). Hemodialysis (HD) was required in 114 patients (17.8 %). 62 patients (9.7 %) died during hospital stay. The percentage of patients with alterations in the different ions was: chlorine 54%, potassium 60.1%, sodium 45.23%, bicarbonate 85.67%, calcium 52.68%, phosphorus 54.49%. The most frequent ionic alterations at a global level were low bicarbonate (78.3%), hyperkalemia (53.05%), hypocalcemia (49.6%) and hyponatremia (41.5%). No significant differences were observed in these percentages when comparing patients with previous CKD with respect to carriers of normal baseline renal function (glomerular filtration rate > 60 ml/min). When analyzing whether electrolyte alterations occurred simultaneously: 2.2% of cases did not present any, 6.3% only one, 18.2% two, 26.4% three, 26.1% four, 14.9% five and 5.9% six simultaneous alterations. In the univariate analysis, patients with hypernatremia (Chi square 22.7; p < 0.001), hyperkalemia (Chi square 9.7; p = 0.008) and hyperphosphatemia (Chi square 18.5; p < 0.001) had higher mortality during admission. In the multivariate analysis using logistic regression, the variables that were independently associated with mortality during hospitalization were phosphorus (OR 1.425; 95% CI 1.212 - 1.676) and chlorine (OR 1.045; 95% CI 1.002 - 1.089). In the follow-up after hospital discharge, the Kaplan-Meier curves in the univariate analysis showed higher mortality in patients who presented hyperkalemia (log rank test: Chi square 15.5; p < 0.0001), hypernatremia (log rank test: Chi square 47.7; p < 0.0001), hypocalcemia (log rank test: Chi square 6.73; p < 0.034) and hyperphosphatemia (log rank test: Chi square 10.24; p < 0.006). In the multivariate analysis using Cox regression, the variables that were independently associated with mortality after hospital discharge were sodium (Exp(B) 1.001; 95% CI 1.002 - 1.048; p = 0.048), potassium (Exp(B) 1.140; 95% CI 1.055 - 1.233; p = 0.001) and phosphorus (Exp(B) 1.087; 95% CI 1.023 - 1.048; p = 0.154). Conclusion In our series of patients with CA-AKI, we detected a high prevalence of electrolyte disorders, without a history of previous CKD having any influence on it. The most frequent was the finding of three or four simultaneous alterations. Phosphorus and chlorine independently influenced mortality during admission. In the follow-up after hospital discharge, sodium, potassium, and phosphorus were independent predictors of mortality. The clinician who treats cases of CA-AKI must expect the appearance of frequent electrolyte disorders and must be prepared for their correct management.

Predictors of Short-term Mortality in Patients of Cirrhosis of Liver Presenting as Acute Kidney Injury: An In-hospital Prospective Observational Study

Acute kidney injury (AKI) is known to be associated with increased short-term mortality among cirrhotic patients. On this background, we designed this study to evaluate various causes of AKI among admitted patients with cirrhosis of liver and predictors of 90-day mortality. One hundred and two consecutive adult patients with cirrhosis of liver with AKI hospitalized between November 2016 and March 2018 were enrolled in this prospective study. Their detailed clinical profile, including biochemical parameters, the etiology of AKI, and their clinical outcome of survival or mortality at 90-days, were recorded. The most common causes of AKI were infections, followed by hypovolemia, seen in 55.88% and 31.37% of the patients, respectively. Hepatorenal syndrome (HRS) was seen in 10.78%, while parenchymal renal disease was the least common (1.9%). The in-hospital mortality rate was 28.4%, while 90-day mortality was 39.21%. The HRS group had a high 90-day mortality rate of 54.54%. ROC analysis of various biochemical parameters revealed that serum creatinine (sCr), Model for End-Stage Liver Disease (MELD), International Normalized Ratio (INR), and Neutrophil-Lymphocyte ratio (NLR), followed by Child Turcotte Pugh (CTP), had high area under the curves of 0.785, 0.773, 0.747, 0.740, and 0.718, respectively, for the prediction of 90-day mortality. Infection is the commonest cause of AKI in cirrhosis; however, mortality in patients with HRS-AKI is higher than that in those with infection-related AKI. Serum creatinine at admission, INR, NLR, and CTP scores predict short-term mortality among patients with AKI in cirrhosis. Further, large prospective studies are needed to confirm these findings.

CARC4: Incidence, Outcomes, and Risk Factors of Acute Kidney Injury in Patients on Percutaneous Mechanical Circulatory Support with Impella 5.0 and 5.5 for Cardiogenic Shock

Purpose: Use of temporary mechanical circulatory devices (tMCS) such as the transaxial flow pump (ImpellaTM. Abiomed, Danvers, MA) for CS-HF is growing. Despite advances in tMCS investigations have found AKI is highly prevalent and strongly associated with mortality in CS patients supported with MCS. We identified pre and post implant risk factors of AKI in CS-HF patients supported with Impella 5.0 and 5.5. Methods: Single center retrospective analysis of 144 Impella 5.0/5.5 devices from 01/2012 to 07/2022 for CS-HF. Patients with non heart failure etiology (n=5) and pre-implant renal replacement therapy (RRT. n=44) were excluded. Demographics and pre-implant chacteristics of patients) as well as post-implant outcomes including mortality, heart replacement therapy (HRT) with ventricular assist device (VAD) or heart transplant (HTX), and native heart survival at discharge were compared between patients with and without acute kidney injury (AKI). AKI was defined as rise in Creatinine 1.5 x baseline or new need for RRT. Logistic regression was used to find independent predictors of post-implant AKI and spearmann correlation was used to find associations with 90-day kidney function defined as fold change in creatine from baseline to peak 90 day values). Results: The final cohort consisted of 96 patients with mean duration of Impella support of 10±12 days.. Of the remaining 96 devices 57 (59.4%) developed AKI with 9 requiring RRT (9.4%). Patients with AKI had higher mortality (42.1% vs 17.9%, p=0.04), lower HRT (43.9% vs 56.4%, p=0.04) and less native heart survival (discharged without HRT) (14.0% vs 25.6%, p=0.04) than those without AKI. Demographics and pre-implant characteristics are shown in in Table 1. Pre-implant creatinine, lactate dehydrogenase (LDH), total bilirubin, Model for End Stage Liver Disease (MELD), and mean right atrial pressure to pulmonary capillary wedge pressure (mRAP/PCWP) as well as post-implant hemolysis (rise in plasma free hemoglobin > 20 or LDH 2.5 x upper limit of normal) were higher in patients with AKI. On logistic regression with backwards selection independent predictors of AKI included pre-implant mRAP/PCWP (OR 33.5 95%CI 1.6-708.8, p=0.02) and post-implant hemolysis (OR 5.6 95%CI 2.1-31.5, p=0.045) (Table 2). On spearman correlation (Table 3) only pre-implant mRAP/PCWP and post-implant LDH:Upper limit of normal LDH were associated with worse long term kidney function defined as fold change of 90-day peak creatinine from baseline. Conclusions: AKI is associated with higher mortality after Impella 5.0 and 5.5 insertion. The etiology of AKI in patients with cardiogenic shock supported by Impella 5.0 and 5.5 is multifactorial but clearly related to venous congestion and hemolysis. Optimization of patient’s fluid status when the device is inserted and avoidance of hemolysis during device support play key roles in reducing AKI in this group of high risk patients.

Single-cell sequencing reveals homogeneity and heterogeneity of the cytopathological mechanisms in different etiology-induced AKI

Homogeneity and heterogeneity of the cytopathological mechanisms in different etiology-induced acute kidney injury (AKI) are poorly understood. Here, we performed single-cell sequencing (scRNA) on mouse kidneys with five common AKI etiologies (CP-Cisplatin, IRI-Ischemia-reperfusion injury, UUO-Unilateral ureteral obstruction, FA-Folic acid, and SO-Sodium oxalate). We constructed a potent multi-model AKI scRNA atlas containing 20 celltypes with 80,689 high-quality cells. The data suggest that compared to IRI and CP-AKI, FA- and SO-AKI exhibit injury characteristics more similar to UUO-AKI, which may due to tiny crystal-induced intrarenal obstruction. Through scRNA atlas, 7 different functional proximal tubular cell (PTC) subtypes were identified, we found that Maladaptive PTCs and classical Havcr1 PTCs but not novel Krt20 PTCs affect the pro-inflammatory and pro-fibrotic levels in different AKI models. And cell death and cytoskeletal remodeling events are widespread patterns of injury in PTCs. Moreover, we found that programmed cell death predominated in PTCs, whereas apoptosis and autophagy prevailed in the remaining renal tubules. We also identified S100a6 as a novel AKI-endothelial injury biomarker. Furthermore, we revealed that the dynamic and active immune (especially Arg1 Macro_2 cells) -parenchymal cell interactions are important features of AKI. Taken together, our study provides a potent resource for understanding the pathogenesis of AKI and early intervention in AKI progression at single-cell resolution.

Comparison of profile and short-term outcome of acute kidney injury between steroid sensitive and steroid resistant nephrotic syndrome

Background: Acute kidney injury (AKI), a severe complication of nephrotic syndrome (NS) is being more prevalent in recent times. Objectives were: 1) Determine incidence, etiology, short term outcome of AKI in children hospitalised with NS. 2) Compare above variables in steroid sensitive nephrotic syndrome (SSNS) versus steroid resistant nephrotic syndrome (SRNS). Methods: Prospective observational study over 18 months including all consecutive nephrotics hospitalized with AKI. AKI defined according to KDIGO criteria with baseline creatinine taken as lowest value in last 6 months/ nadir during stay. Secondary NS were excluded. Demographics, clinical features, labs, hospital course, treatment and follow up at 3 months were recorded. SSNS and SRNS were compared. Results: The incidence of AKI in hospitalised nephrotics (30/304) was 9.8%, 30 patients (16 boys) with mean age 4.08 years (± 4.04 SD). Common etiologies of AKI were infection (60%), nephrotoxic drugs, hypovolemia, and thrombosis in decreasing order. Nephrotics developing AKI had a longer hospital stay versus those without AKI (p<0.001). The 2/30 patients died (6%), 10/30 (33.3%) required PICU, 7/30 (26%) needed RRT. Among discharged patients 4/28(14.28%) had persistent deranged renal functions at 3 months follow up, all of whom belonged to SRNS category. Comparison of 14 patients in SSNS with 16 in SRNS showed UTI (31.3%), drugs (25%), systemic infection (31.3%), thrombosis (12.5%) as etiologies in SRNS. Systemic infection (42.9%), drugs (21.4%), UTI (14.3%) and hypovolemia (21.4%) were causes in SSNS. Mortality rate, need for PICU (p=1.0), RRT (p=1.0) was similar (6%,37.5%, 25%) Vs (7%,28.5%, 21.4%). Conclusions: AKI is seen in up to a tenth of children with NS equally in SSNS and SRNS. While etiology and severity of AKI in the 2 groups is similar, short-term outcome in SRNS is more ominous.

Acute kidney injury post-abdominal surgery in infants: implications for prevention and management.

Acute kidney injury (AKI) is common in critically ill infants and is associated with long-term sequelae including hypertension and chronic kidney disease. The etiology of AKI in infants is multifactorial. There is robust literature highlighting the risk of AKI after cardiothoracic surgery in infants. However, risk factors and outcomes for AKI in infants after abdominal surgery remains limited. This article reviews the epidemiology and association of abdominal surgery with postoperative AKI and suggests methods for AKI management and prevention. Postoperative AKI may result from hemodynamic shifts, hypoxia, exposure to nephrotoxic medications, and inflammation. Infants in the intensive care unit after intraabdominal surgeries have a unique set of risk factors that predispose them to AKI development. Prematurity, sepsis, prolonged operation time, emergent nature of the procedure, and diagnosis of necrotizing enterocolitis increase risk of AKI after intrabdominal surgeries. Prevention, early diagnosis, and management of AKI post-abdominal surgery is imperative to clinical practice. Close monitoring of urine output, serum creatinine, and fluid status is necessary in infants after abdominal surgery. A recent study suggests elevated levels of a urinary biomarker, neutrophil gelatinase-associated lipocalin (NGAL), 24 h after an abdominal procedure may improve early prediction of AKI. Identification of risk factors, avoidance of nephrotoxic medications, careful fluid balance, early detection of AKI, and maintenance of hemodynamic stability is imperative to potentially prevent and/or mitigate AKI.

White paper on mitigating risk factors for acute kidney injury in TAVR: A protocol to decrease TAVR-associated AKI

Acute kidney injury (AKI) after transcatheter aortic valve replacement (TAVR) portends a poor prognosis. In the TVT registry, AKI after TAVR occurred in 10% of the patients. The etiology of AKI after TAVR is multifactorial but contrast volume remains one of the few modifiable risk factors. As patients referred for TAVR have multiple touch points within a siloed healthcare system, there remains an unmet clinical need of a well-defined clinical pathway to minimize the risk of AKI from the time of referral for TAVR to the completion of the procedure. This white paper aims to provide such a clinical pathway.

Clinico-Etiological Spectrum and Outcome in Patients With Septic Acute Kidney Injury and Its Comparison With Non-septic Acute Kidney Injury: A Hospital-Based Prospective Study Conducted in a Tertiary Care Hospital in North India.

Background Acute kidney injury (AKI) is a heterogenous syndrome defined by the impairment of kidney filtration and excretory function over days to weeks, resulting in the retention of nitrogenous and other waste products normally cleared by the kidneys. In addition, AKI is frequently recognized to be associated with sepsis and contributes to an unfavorable outcome in sepsis. This study was undertaken to study and compare the etiology and clinical profile of patients with septic and non-septicAKI and to study and compare the outcome in both groups. Materials and methods This is a prospective, observational, and comparative study with a total sample size of 200 patients selected randomly having sustained an acute kidney injury. Data was collected, recorded, analyzed, and compared for two groups of patients with septic and non-septic AKI. Results A total of 200 cases of AKIwere enrolled, out of which 120 (60%) were due to non-septic etiology and 80 (40%) were of septic etiology. Urosepsis (37.5%) due to various urinary tract infections including pyelonephritis and chest sepsis (18.75%) including community-acquired pneumonia (CAP) and aspiration pneumoniawere the predominant causes of sepsis. AKI secondary to nephrotoxic agents (27.5%) was the commonest cause in the non-septic group, followed by glomerulonephritis (13.3%), vitamin D intoxication-related hypercalcemia (12.5%), acute gastroenteritis (10.8%), etc. Patients of septic AKI had a significantly higher mean of maximum urea and creatinine than their non-septic AKI counterparts. In addition to having an increased duration of hospital stay, mortality was significantly higher in patients with septic AKI (27.5%) than in patients with non-septic AKI (4.1%). However, sepsis had no effect on renal functions, measured by urea and creatinine, at discharge. In patients with AKI, certain factors were found to increase the risk of mortality. These factors include being over 65 years old, needing mechanical ventilation or vasopressors, requiring renal replacement therapy (RRT), and having multiorgan dysfunction syndrome (MODS), septic shock, or acute coronary syndrome (ACS). However, pre-existing conditions such as diabetes, hypertension, malignancy, previous stroke, chronic kidney disease (CKD), and chronic liver disease (CLD) did not affect the overall mortality risk. Conclusion In the septic AKI group, urosepsis was the most frequent etiology of AKI, whilethe most frequent etiology of AKIin the non-septic group was nephrotoxin exposure. Patients with septic AKI had considerably longer hospital stays and greater in-hospital mortality rates than patients with non-septic AKI. The renal functions as determined by urea and creatinine at discharge were unaffected by sepsis. Finally, death was significantly impacted by age of >65 years, the necessity for mechanical ventilation, the use of vasopressors and RRT, and the presence of MODS, septic shock, and ACS.

Diagnostic and prognostic performance of urinary neutrophil gelatinase-associated lipocalin in patients with cirrhosis and acute kidney injury.

Acute kidney injury (AKI) commonly occurs in patients with decompensated cirrhosis. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) could help discriminate between different etiologies of AKI. The aim of this study was to investigate the use of uNGAL in (1) the differential diagnosis of AKI, (2) predicting the response to terlipressin and albumin in patients with hepatorenal syndrome-AKI (HRS-AKI), and (3) predicting in-hospital mortality in patients with AKI. One hundred sixty-two consecutive patients with cirrhosis and AKI were included from 2015 to 2020 and followed until transplant, death, or 90 days. Standard urinary markers and uNGAL were measured. Data on treatment, type, and resolution of AKI were collected. Thirty-five patients (21.6%) had prerenal AKI, 64 (39.5%) HRS-AKI, 27 (16.7%) acute tubular necrosis-AKI (ATN-AKI), and 36 (22.2%) a mixed form of AKI. Mean values of uNGAL were significantly higher in ATN-AKI than in other types of AKI (1162 ng/ml [95% CI 423-2105 ng/ml] vs. 109 ng/ml [95% CI 52-192 ng/ml]; p < 0.001). uNGAL showed a high discrimination ability in predicting ATN-AKI (area under the receiver operating characteristic curve, 0.854; 95% CI 0.767-0.941; p < 0.001). The best-performing threshold was found to be 220 ng/ml (sensitivity, 89%; specificity, 78%). The same threshold was independently associated with a higher risk of nonresponse (adjusted OR [aOR], 6.17; 95% CI 1.41-27.03; p = 0.016). In multivariable analysis (adjusted for age, Model for End-Stage Liver Disease, acute-on-chronic liver failure, leukocytes, and type of AKI), uNGAL was an independent predictor of in-hospital mortality (aOR, 1.74; 95% CI 1.26-2.38; p = 0.001). uNGAL is an adequate biomarker for making a differential diagnosis of AKI in cirrhosis and predicting the response to terlipressin and albumin in patients with HRS-AKI. In addition, it is an independent predictor of in-hospital mortality.

Factors Associated with Mortality and Long-Term Outcomes of Pediatric Acute Kidney Injury in a Resource Limited Setting

Introduction: Despite being a leading cause of morbidity and mortality globally, acute kidney injury (AKI) is worse in resource-limited areas. This study explores AKI incidence, inhospital mortality, and long-term outcomes in resource-limited settings. Methods: This was a prospective study of children with AKI from 2014 to 2019. KDIGO 2012 defined AKI. We assessed the etiology, inhospital mortality, and long-term outcome of AKI in a mission hospital. Results: Only 169 of 201 AKI patients had complete data. The ages ranged from 1.08 months to 17.5 years; 65.7% were male and 65.1% were from lower socioeconomic class. The incidence of AKI was 59.6 cases per 1,000 persons (95% CI: 5.42, 47.1). Most patients had stage 1 KDIGO AKI (91; 53.8%). 1–5 years old had the highest incidence of AKI (65; 38.5%); sepsis (26.6%), severe malaria (15.4%), and nephrotic syndrome (14.8%) were common AKI causes. Fever (72.8%), pallor (52.1%), and vomiting (45.6%) were the most common symptoms. Thirty-two (27.8%) patients had high blood pressure. Inhospital mortality was 14.8% (95% CI: 9.8, 21.1). The cumulative incidence of AKI-related mortality was 93.2 per 1,000 person-years. Poor outcome was associated with breathlessness, hyponatremia, and leukocytosis. Kaplan-Meier survival curve showed 81% (CI: 74–87%) survival after 5 years of AKI. On Cox proportional-hazards analysis, the absence of breathlessness (HR: 2.537, 95%: CI 1.210–5.317) and hyponatremia (HR: 2.914, 95% CI: 1.343–6.324) were associated with increased survival. Conclusion: In resource-limited settings, infectious diseases and nephrotic syndrome are common causes of AKI. Factors associated with mortality include breathlessness and hyponatremia.

Acute kidney injury in diabetes mellitus: Epidemiology, diagnostic, and therapeutic concepts.

Acute kidney injury (AKI) and diabetes mellitus (DM) are public health problems that cause a high socioeconomic burden worldwide. In recent years, the landscape of AKI etiology has shifted: Emerging evidence has demonstrated that DM is an independent risk factor for the onset of AKI, while an alternative perspective considers AKI as a bona fide complication of DM. Therefore, it is necessary to systematically characterize the features of AKI in DM. In this review, we summarized the epidemiology of AKI in DM. While focusing on circulation- and tissue-specific microenvironment changes after DM, we described the active cellular and molecular mechanisms of increased kidney susceptibility to AKI under DM stress. We also reviewed the current diagnostic and therapeutic strategies for AKI in DM recommended in the clinic. Updated recognition of the epidemiology, pathophysiology, diagnosis, and medications of AKI in DM is believed to reveal a path to mitigate the frequency of AKI and DM comorbidity that will ultimately improve the quality of life in DM patients.

Kidney Injury in Children after Hematopoietic Stem Cell Transplant

Hematopoietic cell transplant (HCT), used for treatment of many malignant and non-malignant pediatric diseases, is associated with serious complications, limiting this therapy's benefit. Acute kidney injury (AKI), seen often after HCT, can occur at different stages of the transplant process and contributes to morbidity and mortality after HCT. The etiology of AKI is often multifactorial, including kidney hypoperfusion, nephrotoxicity from immunosuppressive and antimicrobial agents, and other transplant-related complications such as transplant-associated thrombotic microangiopathy and sinusoidal obstructive syndrome. Early recognition of AKI is crucial to prevent further AKI and associated complications. Initial management includes identifying the etiology of AKI, preventing further kidney hypoperfusion, adjusting nephrotoxic medications, and preventing fluid overload. Some patients will require further support with kidney replacement therapy to manage fluid overload and AKI. Biomarkers of AKI, such as neutrophil gelatinase-associated lipocalin can aid in detecting AKI before a rise in serum creatinine, allowing earlier intervention. Long-term kidney dysfunction is also prominent in this population. Therefore, long-term follow-up and monitoring of renal function (glomerular filtration rate, microalbuminuria) is required along with management of hypertension, which can contribute to chronic kidney disease.

Identification of Pre-Renal and Intrinsic Acute Kidney Injury by Anamnestic and Biochemical Criteria: Distinct Association with Urinary Injury Biomarkers.

Acute kidney injury (AKI) is a syndrome of sudden renal excretory dysfunction with severe health consequences. AKI etiology influences prognosis, with pre-renal showing a more favorable evolution than intrinsic AKI. Because the international diagnostic criteria (i.e., based on plasma creatinine) provide no etiological distinction, anamnestic and additional biochemical criteria complement AKI diagnosis. Traditional, etiology-defining biochemical parameters, including the fractional excretion of sodium, the urinary-to-plasma creatinine ratio and the renal failure index are individually limited by confounding factors such as diuretics. To minimize distortion, we generated a composite biochemical criterion based on the congruency of at least two of the three biochemical ratios. Patients showing at least two ratios indicative of intrinsic AKI were classified within this category, and those with at least two pre-renal ratios were considered as pre-renal AKI patients. In this study, we demonstrate that the identification of intrinsic AKI by a collection of urinary injury biomarkers reflective of tubular damage, including NGAL and KIM-1, more closely and robustly coincide with the biochemical than with the anamnestic classification. Because there is no gold standard method for the etiological classification of AKI, the mutual reinforcement provided by the biochemical criterion and urinary biomarkers supports an etiological diagnosis based on objective diagnostic parameters.

Acute Kidney Injury: Medical Causes and Pathogenesis.

Acute kidney injury (AKI) is a common clinical syndrome characterized by a sudden decline in or loss of kidney function. AKI is not only associated with substantial morbidity and mortality but also with increased risk of chronic kidney disease (CKD). AKI is classically defined and staged based on serum creatinine concentration and urine output rates. The etiology of AKI is conceptually classified into three general categories: prerenal, intrarenal, and postrenal. Although this classification may be useful for establishing a differential diagnosis, AKI has mostly multifactorial, and pathophysiologic features that can be divided into different categories. Acute tubular necrosis, caused by either ischemia or nephrotoxicity, is common in the setting of AKI. The timely and accurate identification of AKI and a better understanding of the pathophysiological mechanisms that cause kidney dysfunction are essential. In this review, we consider various medical causes of AKI and summarize the most recent updates in the pathogenesis of AKI.

Herbal medicine in the management of renal disease: A comprehensive review of its potential for acute kidney injury, chronic kidney disease, diabetic nephropathy, and hypertension

Each year, a considerable number of individuals are diagnosed with potentially life-threatening renal failure, encompassing acute kidney injury (AKI) and chronic kidney disease (CKD). New natural herbal compounds, whether used in isolation or combined with medical treatments and an appropriate regime, have been suggested for the management of renal failure. The etiology of AKI remains uncertain; nevertheless, several factors have been proposed as potential causative agents that can lead to renal failure, including renal ischemia-reperfusion injury (IRI), nephrotoxicity, sepsis, administration of radiocontrast agents, and exposure to heavy metal ions. Several commonly utilized herbs with anti-diabetic and antihypertensive properties, known for their antioxidant, anti-inflammatory, and vasorelaxant effects, have been recognized as efficacious therapeutic agents in the management of CKD. The management of renal failure typically involves treating the underlying diseases, such as IRI, sepsis, and diabetes. However, if addressing the root cause is not possible, the focus shifts to managing complications like hypertension and proteinuria.

The effectiveness of locally-prepared peritoneal dialysate in the management of children with acute kidney injury in a south-east Nigerian tertiary hospital.

Peritoneal dialysis (PD) is the preferred mode of renal replacement therapy (RRT) in children with acute kidney injury (AKI). The gold standard remains the use of commercially-prepared PD fluid. In resource-poor nations, its availability and affordability remain a challenge. This study aims to report the effectiveness of locally-prepared PD fluid in the management of AKI in a south-east Nigerian tertiary hospital. This was a retrospective study conducted at the paediatric ward of the University of Nigeria Teaching hospital, Enugu. The case records of 36 children seen over three years, diagnosed with AKI and requiring PD were reviewed. The retrieved information comprised biodata, aetiology of AKI, indications for PD, pre-and post-dialysis estimated glomerular filtration rate (eGFR) and patient outcomes. The children (20 males and 16 females) were aged 3 to 36 months with a mean age of 9.92 ± 6.29 months. The common aetiologies of AKI were septicemia (30.6%), hemolytic uremic syndrome (19.4%), and toxic nephropathy (16.7%). The frequent indications for PD were uremic encephalopathy (58.3%) and severe metabolic acidosis (38.8%). The pre-and post-dialysis mean urine flow rate was 0.16 + 0.13 and 2.77 + 0.56 ml/kg/hour respectively. The eGFR before PD, at discontinuation, and a week later was 6.06 + 2.87, 24.44 + 15.71 and 59.07 + 22.22 mls/min/1.73m2 respectively. PD with locally-prepared dialysate is safe, effective and a life-saving alternative in the management of AKI in children.

Is the Use of Dialysis Associated With an Increased Risk of Death in COVID-19-Related Acute Kidney Injury?

Acute kidney injury (AKI) is frequently reported in the setting of severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection. The aim of our work is to evaluate the impact of acute dialysis use on mortality in patients with AKI during the coronavirus disease 2019 (COVID-19) pandemic. This is a retrospective study conducted in the Hassan II University Hospital of Fez, Morocco. From July 2020 to December 2021, we included all patients admitted to a COVID-19 unit with acute kidney injury defined according to Kidney Disease Improvement Global Outcomes 2012 (KDIGO 2012) criteria. Our patients were older than 18 years, and SARS-CoV-2 infection was confirmed by a positive RT-PCR test or thoracic CT scan imaging. Patients with end-stage renal disease (ESRD) and pregnant women were excluded from our study. The total number of patients hospitalized in the COVID-19 unit during the study period was 2560, including 206 in an intensive care setting. We included 61 patients with AKI, with an incidence in the intensive care unit (ICU) setting of 15.5%. Eighty percent of patients had respiratory distress on admission, which was the main reason for consultation. Stage 1 AKI was found in 1.6% of patients, 25.8% had stage II AKI, and 72.6% had KDIGO stage 3 AKI. The main etiology of AKI was acute tubular necrosis. Lung involvement secondary to infection was severe in 18 patients; 21 had moderate involvement. In our study, twenty-one of our patients (34.4%) were hospitalized in an ICU. Thirteen of our patients were intubated (21.1%). Twenty-one (34.4%) patients were hemodynamically unstable and were put on vasoactive drugs. Twenty-three (37.7%) of our patients received at least one session of conventional acute hemodialysis with an average duration of 2.1 hours ± 0.9 (1-3.5). The indication was overload (27%), severe metabolic acidosis (1.6%), threatening hyperkalemia (1.6%), and symptomatic hyperuremia (62%). The evolution was marked by a return to baseline renal function in two patients, partial improvement in 35 of them at discharge, and no improvement in 24 patients. We recorded a death rate of 34.4% (n=21). In a univariate analysis, we compared the demographic, clinical, paraclinical, and dialytic characteristics of the dialysis and non-dialysis groups. There was a significant difference between unstable, intubated patients and those hospitalized in the ICU in the dialysis group, with respective p-values of p=0.0001, p=0.0001, and p=0.01. We noticed there were more deaths in the dialysis group than in the non-dialysis group; this difference was statistically significant with a p-value of 0.005. In multivariate analysis, a logistic regression model was performed to test the relationship between dialysis and COVID-19 mortality while adjusting for other co-factors. The final model did not show a significant association between dialysis and mortality (p = 0.150, OR: 2.578 [0.710-9.364]). The only factor that remained independently significant was admission to the intensive care unit (p = 0.004, OR: 6.732 [1.847-24.540]). AKI is a frequently encountered complication in patients with COVID-19, especially those hospitalized in the ICU. In the context of the SARS-CoV-2 infection, the use of at least one dialysis session seems to represent an excess risk of mortality related to AKI.

Tertiary lymphoid structure signatures are associated with immune checkpoint inhibitor related acute interstitial nephritis.

Tertiary lymphoid structures (TLSs) are associated with anti-tumor response following immune checkpoint inhibitor (ICI) therapy, but a commensurate observation of TLS is absent for immune related adverse events (irAEs) i.e. acute interstitial nephritis (AIN). We hypothesized that TLS-associated inflammatory gene signatures are present in AIN and performed NanoString-based gene expression and multiplex 12-chemokine profiling on paired kidney tissue, urine and plasma specimens of 36 participants who developed acute kidney injury (AKI) on ICI therapy: AIN (18), acute tubular necrosis (9), or HTN nephrosclerosis (9). Increased T and B cell scores, a Th1-CD8+ T cell axis accompanied by interferon-g and TNF superfamily signatures were detected in the ICI-AIN group. TLS signatures were significantly increased in AIN cases and supported by histopathological identification. Furthermore, urinary TLS signature scores correlated with ICI-AIN diagnosis but not paired plasma. Urinary CXCL9 correlated best to tissue CXCL9 expression (rho 0.75, p < 0.001) and the ability to discriminate AIN vs. non-AIN (AUC 0.781, p-value 0.003). For the first time, we report the presence of TLS signatures in irAEs, define distinctive immune signatures, identify chemokine markers distinguishing ICI-AIN from common AKI etiologies and demonstrate that urine chemokine markers may be used as a surrogate for ICI-AIN diagnoses.

Biochemical Predictors of Acute Kidney Injury in Critically Ill COVID-19 Patients.

It is estimated that 50% of patients with coronavirus disease 2019 (COVID-19) have varying degrees of renal involvement. In this clinical biomarker development research, we examined in a retrospective study design the temporal changes in biochemical laboratory parameters in relation to the development of acute kidney injury (AKI). In a sample of 399 patients admitted from May 2020 to May 2021 to a tertiary health care intensive care unit (ICU), the incidence of AKI was 27.3%, and the median time to AKI was on 7th day of ICU admission. Most common etiology of AKI was kidney hypoperfusion. Within 72 h of developmental of low blood pressure, 63.76% developed AKI. The likelihood of AKI was higher in those with elevated serum ferritin, aspartate transaminase, and thrombocytopenia (low platelet count). A cutoff value of 750.3 ng/mL [area under the ROC curve (AUC) = 0.777] for serum ferritin, and 40.05 U/L for alanine aminotransferase (AUC = 0.677) 1 day before development of AKI displayed, respectively, a sensitivity of 76.2% and 64.3%, whereas the specificity was 69.5% and 64.1%, respectively, for these two biochemical predictors. A cutoff value of platelets (152.50 × 109/L [AUC = 0.75]) measured 4 days before development of AKI, displayed 83.3% sensitivity and 16.4% specificity. Taken together, our study thoroughly examined the temporal association of various clinical and laboratory parameters with AKI and prediction models were developed as per results of the time series data. These observations in a tertiary health care setting contribute to ongoing efforts for biomarker discovery and development using routine biochemical tests so as to forecast AKI in patients with COVID-19.